The potential role of genus Treponema in carcinogenesis with a focus on oral squamous cell carcinoma: a scoping review of the evidence

Current concepts suggest that a dysbiotic environment can promote ‘oral carcinomas.’ Microbiome studies on the oral cavity indicate changes in bacterial disposition in this condition. Yet, few focus on a lesser-known species, Treponema denticola, a motile periodontal pathogen, in addressing concerns related to oral carcinogenesis. Clinical studies find an enrichment of the Treponema genus in sites with oral cancer. Other research designs hint at Treponema denticola possessing both direct and indirect mechanisms to perpetrate damage in oral cancer. We followed the Joanna Briggs Institute (JBI) methodology for this scoping review. The population, Concept and Context (PCC) were as follows: Population: adults with carcinomas in general/OSCC; Concept: T. denticola/Treponema and virulence factors; Context: Presence of T. denticola/Treponema and virulence factors in oral cavity tissues/fluids / or demonstrating role in carcinogenesis. The terms ‘Adult OR population OR patient AND Treponema denticola OR T. denticola OR spirochete* OR treponema* AND oral cancer OR OSCC OR oral squamous cell carcinoma OR carcinoma OR metastasis OR epithelial-mesenchymal transition OR Oral cancer initiation, promotion, progression’ were adapted and searched across four different databases, retrieving all material published in English till 26 August 2024. Sixty-six articles were included in the scoping review following a full-text search, including 35 clinical studies, 21 reviews, 3 database studies, 4 in vitro studies, and 2 animal studies. Approximately 54% of the clinical studies found spirochetes or Treponema (genus/species) or its virulence factor abundant at cancer sites. Animal models also demonstrate the impact of Treponema denticola on tumour progression. The genus Treponema and/or its virulence factors are detected in some oral carcinoma samples, indicating a possible association with advanced stages or deeper invasion. Future research can focus on its ability to induce malignant transformation and explore its potential as a candidate biomarker of oral carcinoma deserving validation.